Deficiency in Factor XII

 

Gene: F12

Transmission: Autosomal, recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation:

Variant 1: Deletion, gene F12; c.1321delC, p.(L441C frame shift, STOP119), exon 11, feline chromosome A1.

Variant 2: Substitution, gene F12; c.1631G>C, p.(G544A), exon 13, feline chromosome A1.

Medical system: blood

Breeds: Balinese, Bengal, Bombay, British Shorthair, Domestic Shorthair, Highland Lynx, Himalayan, Lykoi, Maine Coon, Minuet, Munchkin, Neva Masquerade, Oriental Longhair, Oriental Shorthair, Persian, Ragdoll, Russian Blue, Savannah, Scottish Fold, Selkirk Rex, Siamese, Siberian, Sphynx, Tennessee Rex, Turkish Angora, Turkish Van

Age of onset of symptoms: Asymptomatic but seen when laboratory blood tests for coagulation times are performed.

Factor XII deficiency, also known as Hageman factor deficiency, is a rare genetic blood disorder that results in prolonged clotting of blood observed in vitro, i.e., when laboratory tests are performed. It is caused by a deficiency of factor XII, a protein that acts as a clotting factor at the end of the coagulation cascade and allows blood to clog the site of an injury to stop bleeding.  Although factor XII is necessary for proper blood clotting, when it is deficient, other clotting factors appear to compensate for its absence. Therefore, this genetic defect is considered benign and usually does not present any clinical symptoms in the affected cat. Therefore, this deficiency is usually discovered incidentally during preoperative blood tests or when, in a clotting time evaluation, an increase in activated partial thromboplastin time (APTT) is observed without any other problems related to hemostasis.  A DNA test for the mutation is available.

 

References:

OMIA link: [0364-9685]

Anderson H, Davison S, Lytle KM, et al. (2022) Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.  PLoS Genet. 16;18(6):e1009804.  [pubmed/35709088]

Maruyama H, Brooks MB, Stablein A, et al. (2019) Factor XII deficiency is common in domestic cats and associated with two high frequency F12 mutations. Gene 706:6-12. [pubmed/31022435]

Maruyama H, Hosoe H, Nagamatsu K, et al. (2017) A novel missense mutation in the factor XII gene in a litter of cats with factor XII deficiency. J Vet Med Sci 79:822-826. [pubmed/28392508]

Bender DE, Kloos MT, Pontius JU, et al. (2015) Molecular characterization of cat factor XII gene and identification of a  mutation causing factor XII deficiency in a domestic shorthair cat colony. Vet Pathol 52:312-20. [pubmed/24793828]

 

Contributed by: Alex Raymond-Couturier, Sarah-Maude Paquette, Maëla Larin and Coralie Maheux, Class of 2027, Faculté de médecine vétérinaire, Université de Montréal.   (Translation DWS).